I can understand why many people find the position advanced by the US government in AMP v. PTO (the DOJ amicus brief, discussed in an earlier post) quite appealing. On its face, it seems to offer a reasonable compromise: patent eligibility for "engineered" cDNA, but not for genomic DNA merely "excised" from a human chromosome. However, the distinction is superfical, and does not in my view withstand closer scrutiny.
In particular, the DOJ conveniently ignores the fact that in almost all cases isolation of genomic DNA involves amplification, either through laboratory techniques such as PCR, or by replication in recombinant cells. This distinguishes DNA and RNA from other biomolecules. Prior to the development of recombinant molecular biology in the 1970s, isolation of a naturally occurring biomolecule, such as a protein, involved removing the biomolecule produced in a naturally occurring from other biological constituents. Importantly, all of the purified biomolecule originated in the natural source, and was purified by separating it from other cellular constituents.
In contrast, because DNA can serve as a template for its own replication, DNA is normally isolated by amplifying it many times ("million-fold" is the term used in the amici brief filed by BIO and AUTM). As a result, a typical preparation of "isolated genomic DNA" actually consists primarily of synthetic copies of the genomic DNA molecule.
The DOJ makes much of the fact that a cDNA molecule does not contain the introns, which exist in most human genes, and implies that molecular biologists have "engineered" the introns out. In fact, the introns are naturally removed in the body when genomic DNA is transcribed into mRNA. There is no human engineering involved; production of a cDNA molecule simply entails making a DNA copy of a naturally occurring mRNA and then amplifying it.
In most instances a preparation of isolated genomic DNA comprises synthetic DNA molecules, produced in the laboratory by amplification, that correspond in sequence to a naturally occurring genomic DNA. A preparation of cDNA comprises synthetic DNA molecules, produced in the laboratory by amplification, that correspond in sequence to a naturally occurring mRNA. Considered in this light, I think that the distinction DOJ makes between "excised" genomic DNA versus "engineered" cDNA proves largely illusory.
True, a cDNA molecule has a slightly different chemical structure than the mRNA on which it is based, but the differences are small. The sugar group (ribose) in DNA is lacking an oxygen atom (hence the “deoxy”), and one of the four base groups in RNA (uracil) is slightly different than the corresponding base in DNA (thymine), due to replacement of a methyl group with a hydrogen atom. But mRNA and its corresponding cDNA both encode the same information, and both hybridize to the same complementary strand.
In many instances, a synthetic copy of a genomic DNA molecule is also chemically different from the original. Most naturally occurring genomic DNA is methylated, a form of epigenetic modification, while synthetic copies are often not methylated.
In short, the minor structural difference between cDNA and mRNA is not so qualitatively different than the difference between amplified genomic DNA and genomic DNA of natural origin to warrant using this distinction as the basis for drawing a line between patent eligible and patent ineligible subject matter.